Abstract 17173: Caloric Restriction Protects Against Aging Cardiomyopathy, But Not Longevity
Caloric restriction (CR) is the most common model of enhanced longevity. However, this has been questioned in some mouse models. The goal of this study was to determine if CR protected against aging cardiomyopathy and whether this could account for the enhanced longevity of CR. We studied 2 models of CR, both with 40% calorie reduction; one initiated in 2 month old 129 SVJ mice and continued for 24 months, long term (LT) CR; and the other initiated in mice at 20 months of age, when cardiomyopathy was already developing, and continued for 2 months, short term (ST) CR. The older mice at 2 yrs on normal diet (ND) developed aging cardiomyopathy, compared to young ND mice: left ventricular (LV) systolic function, i.e. LV ejection fraction, was depressed (58±4% vs 71±1%, p<0.05). In addition the cardiomyopathy was characterized by increased myocyte apoptosis (0.29±0.04 vs 0.05±0.02 cells/mm2, p<0.05) and LV hypertrophy (LVH), as evidenced by increased LV/ tibial length (TL) (5.7±0.4 vs 4.6±0.1, p<0.05), compared to young ND mice. With LT CR, aging cardiomyopathy did not develop; LV ejection fraction (71±1%), myocyte apoptosis (0.14±0.07 cells/mm2), and LV/TL (4.2±0.2) were significantly improved compared to old ND mice. Surprisingly, ST CR induced similar salutary effects as LT CR with preserved LV ejection fraction (74±1%), reduced myocyte apoptosis (0.07±0.02 cells/mm2) and LV/TL (5.0±0.2). There were also significant decreases in α-tublin (48%), β-tublin (67%) and cleaved desmin (43%), with an increase in intact desmin (32%), reflecting altered cytoskeletal proteins, as well as an increase in antioxidants MnSOD (31%) and catalase (51%). Even more surprisingly, neither LT, nor ST CR improved longevity; in fact, more mice died with CR (55%), than with ND (45%) over the 2 year monitoring period. Thus, CR prevents the development of aging induced cardiomyopathy, potentially by correcting aging induced alterations in cardiac cytoskeletal proteins and increased resistance to oxidative stress. Of therapeutic relevance, instituting this intervention even in later life can rapidly correct the cardiomyopathy of aging. Surprisingly, CR does not enhance longevity in this mouse model, despite prevention of aging cardiomyopathy.
- © 2011 by American Heart Association, Inc.